肺脏树突状细胞表面共刺激分子在小鼠哮喘模型中的表达

Roles of the costimulatory molecules of pulmonary dendritic cells in the development of asthma

目的通过检测哮喘小鼠肺组织中树突状细胞(dendritic cells,DC)表面共刺激分子的表达以及细胞因子分泌的能力,探讨哮喘发生免疫耐受缺陷的原因。方法Balb/c小鼠60只,分为3组(每组20只):哮喘组、磷酸盐缓冲液(PBS)对照组、健康对照组。对3组小鼠取肺组织做病理观察,行支气管肺泡灌洗液(BALF)计数细胞并分类,ELISA检测血清特异性IgE(sIgE)及BALF中细胞因子的水平。分离、培养肺脏DC,用流式细胞仪(FACS)测CD11c表达,并进一步用FACS分析哮喘小鼠DC表面共刺激分子CD11cCD80、CD11cCD86表达的变化。结果哮喘小鼠肺组织表现为以嗜酸性粒细胞、淋巴细胞浸润为主的炎症改变,BALF中嗜酸性粒细胞计数显著增加(P<0.01),血清sIgE水平显著升高(P<0.01)。与PBS对照组比较,哮喘小鼠CD11cCD80、CD11cCD86表达上调(P<0.01),其分泌IL-10细胞因子的水平明显下降。结论肺脏DC可能通过上调CD11cCD80、CD11cCD86在哮喘的免疫耐受缺陷中发挥作用。

Objective To explore the role of eostimulatory molecules of pulmonary dendritic cells in inducing and modulating immune responses in a murine asthma model. Methods Murine asthma model was established with ovalbumin （OVA） sensitization and challenge, and the model was confirmed by histological analysis of lung tissues. The cell number and differentiation of bronchoalveolar lavage fluid （BALF）, the serum OVA-specific IgE level, and the levels of IL-4, IL-5, and IFN-7 in BALF were detected by ELISA. The purity of pulmonary dendritic cells was assayed by fluorescence-activated cell sorting （FACS） through analyzing CD11c molecule. FACS was also used to measure the ex- pressions of CD11c CD80 and CD11c C86 on pulmonary dendritic cells from OVA-sensitized and challenged mice. Results The histological analysis of lung tissues, the components of BALF, the level of serum OVA-specific IgE, and the production of IL-4, IL-5, and IFN-γ were all consistent with the characteristic of a routine asthma model. The expressions of CD11cCD80 and CD11cCD86 on pulmonary dendritic cells from OVA- sensitized and challenged mice was increased significantly compared with those from PBS-treated mice. On the other hand, the production of IL- 10 and INF-7 by pulmonary dendritic cells from OVA-sensitized and challenged mice were decreased significantly compared with those from PBS-treated mice. Conclusion The results suggest that pulmonary dendritic cells, via upregulafion of CD11cCD50 and CD11cCD86, might play an important role in the regulation of developing and ongoing immune responses in asthma. Dendritic cells in the lung are uniquely situated in the immune cascade to not only initiate but also modulate immune responses.